chr4-163329645-A-G

Position:

• chr4-163329645-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000909.6(NPY1R):​c.-152+2837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,612 control chromosomes in the GnomAD database, including 22,119 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22119 hom., cov: 30)
• Consequence: NPY1R NM_000909.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

NPY1R (HGNC:7956): (neuropeptide Y receptor Y1) This gene belongs to the G-protein-coupled receptor superfamily. The encoded transmembrane protein mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone. The encoded receptor undergoes fast agonist-induced internalization through clathrin-coated pits and is subsequently recycled back to the cell membrane. Activation of Y1 receptors may result in mobilization of intracellular calcium and inhibition of adenylate cyclase activity. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY1R	NM_000909.6	c.-152+2837T>C		intron_variant		ENST00000296533.3	NP_000900.1
NPY1R	XM_005263031.5	c.-151-2940T>C		intron_variant			XP_005263088.1
NPY1R	XM_011532010.4	c.-152+1055T>C		intron_variant			XP_011530312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3	c.-152+2837T>C		intron_variant		1	NM_000909.6	ENSP00000354652.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80171 AN: 151500 Hom.: 22123 Cov.: 30

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.529 AC: 80183 AN: 151612 Hom.: 22119 Cov.: 30 AF XY: 0.526 AC XY: 38979 AN XY: 74058

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.551

Alfa AF: 0.604 Hom.: 27220

Bravo AF: 0.530

Asia WGS AF: 0.478 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.078
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7687423; hg19: chr4-164250797;